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Surgical Pathology Criteria

Gastroesophageal Reflux Disease (GERD)


  • Changes in the gastroesophageal junction and distal esophagus secondary to reflux of gastric or duodenal contents into the esophagus

Diagnostic Criteria

  • There is no gold standard for the diagnosis of GERD
  • All three of the following are required for the diagnosis of GERD
    • Elongated papillae
      • >2/3 of the thickness of the mucosa
      • Requires well oriented specimen
    • Basal cell hyperplasia
      • >15% of the thickness of the mucosa
      • Requires well oriented specimen
    • Intraepithelial granulocytes – at least one of the following is required
      • Neutrophils – any are abnormal
      • Eosinophils
        • Any are abnormal
        • ≥5/HPF raises the possibility of eosinophilic esophagitis
    • If some but not all of these are present, the findings can be considered consistent with or suggestive of reflux
  • Nonspecific findings
    • Capillary dilation and extravasation
    • Intraepithelial lymphocytes
    • Ballooning degeneration of squamous cells
    • Multinucleated squamous cells
    • Mild chronic inflammation is nearly always present the gastroesophageal junction
  • Identification of ulceration should prompt close evaluation and possibly stains for viruses, including Herpes and CMV
  • Identification of neutrophils in the squamous mucosa should prompt a stain for fungi such as Candida
  • Identification of neutrophils in the glandular mucosa should prompt close evaluation and stain for Helicobacter unless an accompanying gastric antral biopsy is available for assessment
  • Identification of goblet cells may indicate Barrett esophagus
  • Pancreatic metaplasia is seen frequently in biopsies from the EGJ
    • It is not clear if this represents metaplasia or heterotopia
    • No clinical significance

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting : November 11, 2009

Differential Diagnosis

Gastroeophageal Reflux vs Eosinophilic Esophagitis
Intraepithelial Eosinophils Diagnosis
≥15-20/HPF Marked intraepithelial eosinophilia consistent with eosinophilic esophagitis if other causes are ruled out (see below)
5-14/HPF Indeterminate for eosinophilic esophagitis
<5/HPF Consistent with reflux
Eosinophils are assessed in the single most involved field


Eosinophilic GI disorders by location

Eosinophilic Esophagitis Eosinophilic Gastroenteritis Eosinophilic Proctocolitis
Confined to esophagus Involves stomach and/or small intestine Confined to rectum and colon
Good response to dietary manipulation Poor response to dietary manipulation Good response to dietary manipulation


Eosinophils may be numerous in other diseases

  • Food impaction must be ruled out clinically
  • Lodging of medicinal agents (pill esophagitis) must be ruled out clinically
  • Drug related must be ruled out clinically
  • Hypereosinophilic syndrome
    • Requires >1500 eosinophils / microliter
  • Parasitic disease must be ruled out by stool examination
  • Crohn disease
    • May contain many eosinophils in the infiltrate but they do not predominate
    • Very rare in esophagus
  • Milk protein enteropathy must be ruled out clinically especially in infants
  • Systemic diseases
    • Churg Strauss vasculitis
    • Polyarteritis nodosa
    • Scleroderma
    • Stevens-Johnson syndrome


  • Endoscopic appearance is variable
    • May be normal
    • Erosions, ulceration, exudate
    • Stricture, Schatzi ring


  • Noffsinger A, Fenoglio-Preiser CM, Maru D, Gilinisky N.  Gastrointestinal Diseases, AFIP Atlas of Nontumor Pathology, First Series, Fascicle 5, 2007.
  • Wang HH, Zeroogian JM, Spechler SJ, Goyal RK, Antonioli DA. Prevalence and significance of pancreatic acinar metaplasia at the gastroesophageal junction. Am J Surg Pathol. 1996 Dec;20(12):1507-10.
  • Parfitt JR, Gregor JC, Suskin NG, Jawa HA, Driman DK. Eosinophilic esophagitis in adults: distinguishing features from gastroesophageal reflux disease: a study of 41 patients. Mod Pathol. 2006 Jan;19(1):90-6.
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